(1) Field of the Invention
The present invention relates to new anthracycline derivatives and a process for their preparation. More particularly, the present invention relates to new anthracycline derivatives, .beta.-rhodomycinone-RDA, .beta.-rhodomycinone-RDRs and .beta.-rhodomycinone-RD, to the process for the preparation thereof by reduction or acid hydrolysis of .beta.-rhodomycinone-RDC and to the methods for their recovery and purification.
(2) Description of the Prior Art
A number of anthracycline glycosides have been found in the culture medium of Streptomyces, and are desribed in prior literatures. Among them, daunomycin and adriamycin have already been clinically applied to human cancers.
Rhodomycinones, iso-rhodomycinone and rhodomycin-related antibiotics are described in Chem. Ber. 88, 1792-1818 (1955); Chem. Ber. 101, 1341-1348 (1968); J. Med. Chem., 20, 957-960 (1977); Pharmacie 27, 782-789 (1972); Zeit. Allg. Mikrobiol., 14, 551-558 (1974); Tetrahed. Lett. No. 38, 3699-3702 (1973); Folia Microbiol., 24, 293-295 (1979) and J. Antibiotics, 32, 420 (1979).
Aclacinomycin A is disclosed in U.S. Pat. No. 3,988,315 and by Oki et al. in J. Antibiotics 28, 830 (1975) and 32, 791-812 (1979).
Cinerubins A and B are disclosed in U.K. Pat. No. 846,130, U.S. Pat. No. 3,864,480, Keller-Schierlein et al., "Antimicrobial Agents and Chemotherapy", page 68 (1970), Chemical Abstracts 54, 1466i (1960) and J. Antibiotics 28, 830 (1975).
Further illustrative and summary disclosures of anthracycline antibiotics can be located in the Index of Antiobiotics from Actinomycetes, Hamao Umezawa, Editor-in-Chief, University Park Press, State College, Pa., U.S.A. (1967) as follows:
______________________________________ Antibiotics Page Numbers ______________________________________ Aclacinomycins A and B 101-102 Adriamycin 122 Carminomycin I 225 Galirubins S - D 405-408 Rhodomycins X - Y 879-880 .beta.-Rhodomycins 881-885 .gamma.-Rhodomycins 886-892 Steffimycin 945 ______________________________________
The textbook, Antibiotics, Volume 1, Mechanism of Action, edited by David Gottlieb and Paul D. Shaw, Springer-Verlag New York, Inc., N.Y. (1967) at pages 190-210, contains a review by A. Dimarco entitled "Daunomycin and Related Antibiotics".
Information Bulletin, No. 10, International Center of Information of Antibiotics, in collaboration with WHO, December, 1972, Belgium, reviews anthracyclines and their derivatives.
Furthermore, new anthracycline glycoside derivatives of rhodomycin-group, .epsilon.-rhodomycin-RDC, .epsilon.-isorhodomycin-RDC, .beta.-rhodomycin-RDC, .gamma.-rhodomycin-RDC and .beta.-pyrromycin-RDC and a process for the production thereof by microbiological conversion method are disclosed (U.S. Pat. No. 4,316,011).